Role of mitotic, pro-apoptotic and anti-apoptotic factors in human kidney development
The expression pattern of mitotic Ki-67 and anti-apoptotic bcl-2 proteins, as well as apoptotic caspase-3 and p53 proteins, were investigated in the human mesonephros and metanephros of 5–9 week-old human conceptuses. Apoptotic cells were additionally detected using the terminal deoxynucleotidyl transferase (TdT) nick-end labelling (TUNEL) method. Between the 5th and 7th developmental weeks Ki-67, caspase-3 and TUNEL-positive cells characterized all mesonephric structures, indicating importance of cell proliferation in the growth of the mesonephros and role of apoptosis in nephrogenesis. From the 7th week on, p53 and bcl-2 positive cells appeared in the mesonephros as well. Regressive changes in the mesonephros could be regulated by activation of p53, while bcl-2 could contribute to selective survival of some tubules giving rise to adult structures. In the early human metanephros (5–7 weeks), Ki-67 positive cells characterized all metanephric structures, indicating a role of cell proliferation in branching of the ureteric bud and in nephron formation. During the same period bcl-2, caspase-3 and TUNEL-positive cells were found only in the metanephric mesenchyme and nephrons. Bcl-2 protein probably protected nephrons from apoptosis, while caspase-3 protein controlled cell death in the mesenchyme. At later stages (7–9-weeks), appearance of p53-expressing cells could participate in further morphogenesis of the metanephric collecting system. The factors investigated had a spatially and temporally restricted pattern of appearance in developing kidneys. Changes in that pattern might lead to serious disturbances of kidney formation and function in early childhood.
KeywordsHuman embryo Kidney development Mesonephros Metanephros
We are grateful to Mrs. Asja Miletiæ for her skilful technical assistance. This work was supported by the Ministry of Science, Education and Sports of the Republic of Croatia (grants no. 0216002 and 0216001).
- 2.Sadler TW (1985) Langman’s medical embryology, 5th edn. Williams & Wilkins, Baltimore, pp 247–280Google Scholar
- 5.Alison MR, Sarraf CE (1992) Apoptosis: a gene-directed programme of cell death. J R Coll Phys Lond 26:25–35Google Scholar
- 17.Kamada S, Shimono A, Shinto Y, Tsujimura T, Takahashi T, Noda T, Kitamura Y, Kondoh H, Tsujimoto Y (1995) Bcl-2 deficiency in mice leads to pleiotropic abnormalities: accelerated lymphoid cell death in thymus and spleen, polycystic kidney, hair hypopigmentation, and distorted small intestine. Cancer Res 55:354–359PubMedGoogle Scholar
- 24.Lichnovsky V, Erdosova B, Punkt K, Zapletal M (1999) Expression of bcl-2 in the developing kidney of human embryos and fetuses: qualitative and quantitative study. Acta Univ Palacki Olomuc Fac Med 142:61–64Google Scholar
- 32.Potter EL (1972) Normal and abnormal development of the kidney. Year Book Medical Publishers, Chicago, pp 3–79Google Scholar
- 33.Moore KL (1989) Before we are born: basic embryology and birth defects, 3rd edn. Saunders, Philadelphia, pp 180–199Google Scholar